Effects of HIV-1 TAT protein and methamphetamine exposure on visual discrimination and executive function in mice

Behav Brain Res. 2018 Sep 3:349:73-79. doi: 10.1016/j.bbr.2018.04.046. Epub 2018 Apr 27.

Abstract

Mild neurocognitive impairments are common in people with human immunodeficiency virus (HIV) infection. HIV-encoded proteins, such as trans-activator of transcription (TAT), contribute to neuropathology and cognitive function in medicated subjects. The combination of TAT and comorbid methamphetamine use may further impair neurocognitive function in HIV-positive individuals by affecting dopaminergic systems in the brain. The current study examined the effects of TAT protein expression and methamphetamine exposure on cognitive function and dopamine systems in mice. Transgenic mice with inducible brain expression of the TAT protein were exposed to a binge methamphetamine regimen. TAT expression was induced via a doxycycline-containing diet during the final stage of the regimen and maintained throughout cognitive testing. Learning and executive function were assessed using an operant visual discrimination protocol, with a strategy switch and reversal. TAT expression and methamphetamine exposure improved visual discrimination learning. Combined TAT expression and methamphetamine exposure increased perseverative errors during reversal learning. TAT expression altered reversal learning by improving early stage, but impairing late stage, learning. TAT expression was also associated with an increase in dopamine transporter expression in the caudate putamen. These results highlight that TAT expression and methamphetamine exposure likely affect a range of selective cognitive processes, with some potentially improving function under certain conditions.

Keywords: Dopamine transporter; Methamphetamine binge; Perseveration; Reversal learning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / complications
  • AIDS Dementia Complex / metabolism
  • Amphetamine-Related Disorders / psychology*
  • Animals
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Caudate Nucleus / virology
  • Cognition Disorders / etiology*
  • Cognition Disorders / metabolism
  • Discrimination, Psychological* / drug effects
  • Discrimination, Psychological* / physiology
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Executive Function* / drug effects
  • Executive Function* / physiology
  • HIV-1
  • Male
  • Methamphetamine / toxicity*
  • Mice, Transgenic
  • Putamen / drug effects
  • Putamen / metabolism
  • Putamen / virology
  • Reversal Learning / drug effects
  • Reversal Learning / physiology
  • Visual Perception / drug effects
  • Visual Perception / physiology
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Methamphetamine